The overall objective of the present research is to determine the role of chromatin structure and function in the radio-response of mammalian cells. With regard to function, the goal is to determine if addition, replacement or chemical modification of chromosomal proteins play a role in the x-ray induced G2-block. With regard to chromatin structure, the goal is to determine if hyperthermia induces changes in the chromatin structure and if these changes play a role in the heat-induced radiosensitization of mammalian cells. Recent evidence suggests that the chromatin complex may be the target for x-ray induced mitotic delay. Also, several laboratories have shown that protein synthesis is required for cells to overcome the block and complete mitosis. Thus, it is reasonable to determine if an alteration in the chromatin structure occurs during the G2 block. Our preliminary results show that heat, which increases radiolethality, causes increase in the protein/DNA ratio of the mammalian chromatin. This phenomenon may play a role in the heat and radiation synergism.